Reflecting our clinical interests, the proposed research concerns brain metabolism in young mice (newborn and developing) in vivo. Objectives are a better understanding of the pathogenesis of common serious clinical diseases relating to the central nervous system in infants and children and a biochemical rationale for specific or other therapy. In experimental models of acute water intoxication and chronic hypernatremic dehydration in young mice we have found a direct relationship of plasma sodium concentration and brain amino acid levels. To determine the mechanism of this finding we will study brain amino acid metabolism in these two syndromes. We have found that acute salt poisoning in young mice induces hypoglycemia and reduces the brain glucose content. To determine the pathophysiology of this association we will study glucose uptake and glucose metabolism in muscle and measure plasma insulin levels. Effects on brain carbohydrate and energy metabolism will also be examined. Relevant to the widespread use of methylxanthines in apnea of prematurity we have initiated studies of aminophylline action in developing mouse brain. In weanling mice aminophylline increased brain cyclic nucleotide levels and cerebral metabolic rate. We will study this relationship in local regions of brain in vivo. In neonatal mice aminophylline (in a dose used in premature infants) decreased anoxic survival. To determine the mechanism of this adverse reaction we will determine cerebral metabolic rate in the younger mice and measure the brain energy reserve during anoxia.